Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-13
Ruschitzka, F T; Wenger, R H; Stallmach, T; Quaschning, T; de Wit, C; Wagner, K; Labugger, R; Kelm, M; Noll, G; Rülicke, T; Shaw, S; Lindberg, R L; Rodenwaldt, B; Lutz, H; Bauer, C; Lüscher, T F; Gassmann, M (2000). Nitric oxide prevents cardiovascular disease and determines survival in polyglobulic mice overexpressing erythropoietin. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 97(21):11609-11613.
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Nitric oxide (NO) induces vasodilatatory, antiaggregatory, and antiproliferative effects in vitro. To delineate potential beneficial effects of NO in preventing vascular disease in vivo, we generated transgenic mice overexpressing human erythropoietin. These animals induce polyglobulia known to be associated with a high incidence of vascular disease. Despite hematocrit levels of 80%, adult transgenic mice did not develop hypertension or thromboembolism. Endothelial NO synthase levels, NO-mediated endothelium-dependent relaxation and circulating and vascular tissue NO levels were markedly increased. Administration of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) led to vasoconstriction of peripheral resistance vessels, hypertension, and death of transgenic mice, whereas wild-type siblings developed hypertension but did not show increased mortality. L-NAME-treated polyglobulic mice revealed acute left ventricular dilatation and vascular engorgement associated with pulmonary congestion and hemorrhage. In conclusion, we here unequivocally demonstrate that endothelial NO maintains normotension, prevents cardiovascular dysfunction, and critically determines survival in vivo under conditions of increased hematocrit.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology|
|DDC:||610 Medicine & health|
|Date:||10 October 2000|
|Deposited On:||11 Feb 2008 13:11|
|Last Modified:||29 Nov 2013 20:08|
|Publisher:||National Academy of Sciences|
|Free access at:||Publisher DOI. An embargo period may apply.|
|Citations:||Web of Science®. Times Cited: 151|
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